Bordetella pertussis exhibits genomic diversity within patients and laboratory culture

ABSTRACT Over the past decade, genomic characterization of Bordetella pertussis isolates recovered from US pertussis patients has unveiled noteworthy structural gene order variations. Whole-genome sequencing (WGS) shows that although B. pertussis exhibits little gene sequence variation, genomes from...

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Main Authors: E. Bouda, Y. Peng, M. M. Williams, P. K. Cassiday, T. H. Skoff, H. Ju, H. Fueston, D. Kurien, D. Morales, M. Cole, E. A. Travanty, D. Santoro, P. M. Snippes Vagnone, K. Mitchell, M. Martinez, Y. Unoarumhi, M. Bentz, S. Nobles, J. Heuser, M. L. Tondella, L. C. Pawloski, M. R. Weigand
Format: Article
Language:English
Published: American Society for Microbiology 2025-07-01
Series:mSystems
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Online Access:https://journals.asm.org/doi/10.1128/msystems.01717-24
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author E. Bouda
Y. Peng
M. M. Williams
P. K. Cassiday
T. H. Skoff
H. Ju
H. Fueston
D. Kurien
D. Morales
M. Cole
E. A. Travanty
D. Santoro
P. M. Snippes Vagnone
K. Mitchell
M. Martinez
Y. Unoarumhi
M. Bentz
S. Nobles
J. Heuser
M. L. Tondella
L. C. Pawloski
M. R. Weigand
author_facet E. Bouda
Y. Peng
M. M. Williams
P. K. Cassiday
T. H. Skoff
H. Ju
H. Fueston
D. Kurien
D. Morales
M. Cole
E. A. Travanty
D. Santoro
P. M. Snippes Vagnone
K. Mitchell
M. Martinez
Y. Unoarumhi
M. Bentz
S. Nobles
J. Heuser
M. L. Tondella
L. C. Pawloski
M. R. Weigand
author_sort E. Bouda
collection DOAJ
description ABSTRACT Over the past decade, genomic characterization of Bordetella pertussis isolates recovered from US pertussis patients has unveiled noteworthy structural gene order variations. Whole-genome sequencing (WGS) shows that although B. pertussis exhibits little gene sequence variation, genomes from clinical isolates frequently differ in gene order through rearrangement between insertion sequence elements. To better understand rates of genome rearrangement and single nucleotide polymorphism (SNP) in B. pertussis, intra-patient genomic diversity was examined. Five states submitted, on average, five isolates per patient specimen following culture confirmation to the US Centers for Disease Control and Prevention for molecular characterization. Analysis of 149 patient specimen sets revealed only rare SNP variation, while isolate sets from 12 patients included genomic rearrangements that did not impact vaccine antigen production. To investigate the frequency and stability of such rearrangements during laboratory culture, replicate cultures of two pairs of isolates differing by duplication and inversion were subcultured for eight serial passages. WGS confirmed the initial presence of rare duplication mutations that became dominant in later passages, as well as the stable maintenance of a large, inverted genomic region during passage. These findings suggest that B. pertussis exhibits genomic diversity within a single clinical diagnostic specimen and acquires genomic variations during serial laboratory passages, indicative of bacterial genomic plasticity. Importantly, these rearrangements did not impact the frequency or distribution of SNPs. These results underscore the importance of minimizing the laboratory passaging of clinical isolates used for infectious disease surveillance.IMPORTANCEThe whooping cough-causing bacterium Bordetella pertussis can alter its genetic structure while conserving areas essential for vaccine efficacy. By examining B. pertussis from infected patients, we demonstrate the significance of reducing laboratory manipulation of bacteria to maintain reliable monitoring data from laboratory cultures. Public health officials can use these data to develop efficient disease control tactics and better understand B. pertussis’s adaptability. This study highlights the importance of immunizations and the necessity of thorough genetic surveillance in the fight against this chronic and avoidable respiratory illness.
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spelling doaj-art-df46e0571288460b8a71c65a368d76bf2025-08-20T03:30:15ZengAmerican Society for MicrobiologymSystems2379-50772025-07-0110710.1128/msystems.01717-24Bordetella pertussis exhibits genomic diversity within patients and laboratory cultureE. Bouda0Y. Peng1M. M. Williams2P. K. Cassiday3T. H. Skoff4H. Ju5H. Fueston6D. Kurien7D. Morales8M. Cole9E. A. Travanty10D. Santoro11P. M. Snippes Vagnone12K. Mitchell13M. Martinez14Y. Unoarumhi15M. Bentz16S. Nobles17J. Heuser18M. L. Tondella19L. C. Pawloski20M. R. Weigand21Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USADivision of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USADivision of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USADivision of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USADivision of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USADivision of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USADivision of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USAASRT, Inc., Atlanta, Georgia, USAASRT, Inc., Atlanta, Georgia, USADivision of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USAColorado State Public Health Laboratory, Denver, Colorado, USAPublic Health Laboratory, Connecticut Department of Public Health, Rocky Hill, Connecticut, USAPublic Health Laboratory Division, Minnesota Department of Health, Saint Paul, Minnesota, USA,New York State Public Health Laboratory, New York, New York, USAOregon State Public Health Laboratory, Hillsboro, Oregon, USADivision of Core Laboratory Services and Response, Office of Laboratory Systems and Response, Centers for Disease Control and Prevention, Atlanta, Georgia, USADivision of Core Laboratory Services and Response, Office of Laboratory Systems and Response, Centers for Disease Control and Prevention, Atlanta, Georgia, USADivision of Core Laboratory Services and Response, Office of Laboratory Systems and Response, Centers for Disease Control and Prevention, Atlanta, Georgia, USAASRT, Inc., Atlanta, Georgia, USADivision of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USADivision of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USADivision of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USAABSTRACT Over the past decade, genomic characterization of Bordetella pertussis isolates recovered from US pertussis patients has unveiled noteworthy structural gene order variations. Whole-genome sequencing (WGS) shows that although B. pertussis exhibits little gene sequence variation, genomes from clinical isolates frequently differ in gene order through rearrangement between insertion sequence elements. To better understand rates of genome rearrangement and single nucleotide polymorphism (SNP) in B. pertussis, intra-patient genomic diversity was examined. Five states submitted, on average, five isolates per patient specimen following culture confirmation to the US Centers for Disease Control and Prevention for molecular characterization. Analysis of 149 patient specimen sets revealed only rare SNP variation, while isolate sets from 12 patients included genomic rearrangements that did not impact vaccine antigen production. To investigate the frequency and stability of such rearrangements during laboratory culture, replicate cultures of two pairs of isolates differing by duplication and inversion were subcultured for eight serial passages. WGS confirmed the initial presence of rare duplication mutations that became dominant in later passages, as well as the stable maintenance of a large, inverted genomic region during passage. These findings suggest that B. pertussis exhibits genomic diversity within a single clinical diagnostic specimen and acquires genomic variations during serial laboratory passages, indicative of bacterial genomic plasticity. Importantly, these rearrangements did not impact the frequency or distribution of SNPs. These results underscore the importance of minimizing the laboratory passaging of clinical isolates used for infectious disease surveillance.IMPORTANCEThe whooping cough-causing bacterium Bordetella pertussis can alter its genetic structure while conserving areas essential for vaccine efficacy. By examining B. pertussis from infected patients, we demonstrate the significance of reducing laboratory manipulation of bacteria to maintain reliable monitoring data from laboratory cultures. Public health officials can use these data to develop efficient disease control tactics and better understand B. pertussis’s adaptability. This study highlights the importance of immunizations and the necessity of thorough genetic surveillance in the fight against this chronic and avoidable respiratory illness.https://journals.asm.org/doi/10.1128/msystems.01717-24Bordetella pertussisgenomic rearrangementsgenomic variationsgenetic polymorphismswhole genome sequencinggenome typing
spellingShingle E. Bouda
Y. Peng
M. M. Williams
P. K. Cassiday
T. H. Skoff
H. Ju
H. Fueston
D. Kurien
D. Morales
M. Cole
E. A. Travanty
D. Santoro
P. M. Snippes Vagnone
K. Mitchell
M. Martinez
Y. Unoarumhi
M. Bentz
S. Nobles
J. Heuser
M. L. Tondella
L. C. Pawloski
M. R. Weigand
Bordetella pertussis exhibits genomic diversity within patients and laboratory culture
mSystems
Bordetella pertussis
genomic rearrangements
genomic variations
genetic polymorphisms
whole genome sequencing
genome typing
title Bordetella pertussis exhibits genomic diversity within patients and laboratory culture
title_full Bordetella pertussis exhibits genomic diversity within patients and laboratory culture
title_fullStr Bordetella pertussis exhibits genomic diversity within patients and laboratory culture
title_full_unstemmed Bordetella pertussis exhibits genomic diversity within patients and laboratory culture
title_short Bordetella pertussis exhibits genomic diversity within patients and laboratory culture
title_sort bordetella pertussis exhibits genomic diversity within patients and laboratory culture
topic Bordetella pertussis
genomic rearrangements
genomic variations
genetic polymorphisms
whole genome sequencing
genome typing
url https://journals.asm.org/doi/10.1128/msystems.01717-24
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